Axitinib

SKU: orb1308579

Description

Axitinib (AG-013736) is a potent, multi-targeted tyrosine kinase inhibitor with IC50 values of 4, 20, 0.4, and 2 nM for VEGFR1, VEGFR2, VEGFR3, and PDGFRβ, respectively. It exhibits significant antitumor activity and is an approved therapeutic for renal cell carcinoma, widely used in preclinical angiogenesis and oncology research both in vitro and in vivo.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 319460-85-0
• MW: 386.47
• Purity: 99.81% (May vary between batches)
• Formula: C₂₂H₁₈N₄OS
• SMILES: C(=C/C1=CC=CC=N1)\C=2C=3C(=CC(SC4=C(C(NC)=O)C=CC=C4)=CC3)NN2
• Target: PDGFR,c-Kit,VEGFR
• Solubility: DMSO:23.2 mg/mL (60.03 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.18 mM)

Bioactivity

• Target IC50:
  VEGFR3:0.1-0.3 nM|PDGFRβ:1.6 nM|VEGFR2/KDR:0.2 nM|VEGFR1/FLT1:0.1 nM|VEGFR2/Flk1:0.18 nM|c-Kit:1.7 nM
• In Vivo:
  METHODS: To assay antitumor activity in vivo, Tepotinib (5-15 mg/kg) was injected once daily for 14 days into CD-1 mice bearing EBC-1 xenografts. RESULTS: Administration of 5 or 15 mg/kg of Tepotinib daily to mice bearing EBC-1 tumors effectively inhibited or completely regressed the tumors, respectively.
• In Vitro:
  METHODS: Thirteen neuroblastoma cells were treated with Tepotinib for 72 h and cell viability was measured by MTT assay. RESULTS: All cells showed reduced cell viability with IC50 values ranging from 2.4-8.5 µM. METHODS: EBC-1 cells were treated with Tepotinib (0-30 µmol/L) for 3 days, and the expression levels of target proteins were detected by Western Blot. RESULTS: Tepotinib treatment induced a significant reduction in c-Met constitutive phosphorylation in EBC-1 cells with an IC50 of 9 nmol/L. Tepotinib also effectively blocked the phosphorylation of the major downstream effectors of the c-Met enzyme in EBC-1, MKN-45, and Hs746T cells in the 1-10 nmol/L range.
• Cell Research:
  Endothelial or tumor cells were starved for 18 h in the presence of either 1% FBS (HUVEC) or 0.1% FBS (tumor cells). Axitinib was added and cells were incubated for 45 min at 37°C in the presence of 1 mmol/L Na3VO4. The appropriate growth factor was added to the cells, and after 5 min, cells were rinsed with cold PBS and lysed in the lysis buffer and a protease inhibitor cocktail. The lysates were incubated with immunoprecipitation antibodies for the intended proteins overnight at 4°C. Antibody complexes were conjugated to protein A beads and supernatants were separated by SDS-PAGE. The Super Signal West Dura kit was used to detect the chemiluminescent signal .
• Animal Research:
  AG-013736, a receptor kinase inhibitor of VEGFRs and, at higher doses, PDGFRs (IC50 = 0.1 nmol/L for VEGFR-1, 0.2 nmol/L for VEGFR-2, 0.1–0.3 nmol/L for VEGFR-3, and 1.6 nmol/L for PDGFRβ; ref. 18), was provided by Pfizer Global Research and given once daily by gavage in a volume of 0.13 mL. Control animals received 0.5% carboxymethylcellulose drug carrier. Irradiations were done on nonanesthetized mice using a 137Cs source operating at 2.4 Gy/min. Mice were confined to plastic jigs with tumor-bearing legs extended through an opening in the side, allowing local irradiations. Fractionated doses were given in five daily 2 Gy fractions per week (omitting weekends). For combination treatments, radiotherapy was delivered first, and AG-013736 was given within ～4 h. Mice were sacrificed, and tumors were excised and then quick frozen (using liquid nitrogen) following 1, 2, or 3 weeks of treatment .

Storage & Handling

• Storage: store at low temperature,keep away from moisture,keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

cKit, c-kit, Axitinib, AG 013736, AG013736, AG-013736, inhibit, PDGFRβ, Platelet-derived growth factor receptor, PDGFR, Inhibitor, VEGFR, VEGFR3, VEGFR2, VEGFR1, Vascular endothelial growth factor receptor

Compound Identifiers

PubChem CID

6450551